Molluscan hearts are modulated by numerous cardioexcitatory agents such as the neuropeptide FMRFamide and neurotransmitter, 5-hydroxytryptamine (5HT). The current project, using as the primary technique self-referencing calcium electrodes, studied mechanisms by which 5HT mobilizes calcium from various cellular compartments to enhance the contractility of ventricular muscle. Treatment of isolated muscle bundles, trabeculae, from the inner wall of the gastropod ventricle with micromolar concentrations of 5HT caused transient calcium efflux. This efflux was probably the result of a previous influx of calcium through L-type calcium channels and reflects rapid extrusion mechanisms by the sarcolemma of the cardiac myocytes. A similar effect has been previously described in the cardiac preparation in response to FMRFamide (Devlin, 1997). However, there are pronounced differences between the efflux stimulated by 5HT and that of FMRFamide. 5HT-induced efflux was typically a small, short-lived transient, whereas FMRFamide caused not only a more sustained efflux but it was of larger magnitude. To test the hypothesis that calcium was first entering through voltage-gated L-type channels, verapamil (a calcium channel blocker) and Bay K 8644 (a channel agonist) were tested. Neither verapamil nor Bay K 8644 had any effect on spontaneous efflux. Verapamil however inhibited calcium efflux stimulated by 5HT, whereas Bay K 8644 potentiated the efflux. These data corroborate earlier findings (Devlin, 1997) that found invertebrate muscle to be sensitive to mammalian L-type channel, and is further evidence in support of a use-dependent mechanism by calcium channel drugs. A Na+-free, lithium-substituted saline, or benzamil, were used to study the role of the Na/Ca exchanger in calcium efflux. Treatment of the trabeculae with a Na+-free, lithium-substituted saline had no effect on spontaneous calcium efflux, but greatly inhibited 5HT-induced efflux. Benzamil caused a sustained calcium influx that was slightly potentiated by simultaneous treatment with 5HT. Treatment of the trabeculae with cyclopiazonic acid, an inhibitor of the SR calcium ATPase, completely eliminated any calcium efflux stimulated by 5HT. This data suggests that 5HT may use the SR as its' primary calcium reservoir during the process of E-C coupling in this muscle. Devlin, C.L. 1997. A vibrating Ca2+-selective electrode measures Ca2+ flux induced by the neuro-peptide FMRFamide in a gastropod ventricle. Comp. Biochem. Physiol. 116A: 93-100.